[ CAS No. 952479-65-1 ] {[proInfo.proName]}

Name: 952479-65-1|Methyl 2H-indazole-7-carboxylate|97%
Brand: Ambeed
SKU: A102548
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Quality Control of [ 952479-65-1 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 952479-65-1 ]

Product Details of [ 952479-65-1 ]

CAS No. :	952479-65-1	MDL No. :	MFCD22683960
Formula :	C₉H₈N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GEWJEKADAXWFPY-UHFFFAOYSA-N
M.W :	176.17	Pubchem ID :	24728931
Synonyms :

Calculated chemistry of [ 952479-65-1 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.11
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	47.37
TPSA :	54.98 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.37 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.18
Log Po/w (XLOGP3) :	1.41
Log Po/w (WLOGP) :	1.35
Log Po/w (MLOGP) :	1.04
Log Po/w (SILICOS-IT) :	1.84
Consensus Log Po/w :	1.36

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.2
Solubility :	1.11 mg/ml ; 0.0063 mol/l
Class :	Soluble
Log S (Ali) :	-2.17
Solubility :	1.19 mg/ml ; 0.00678 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.98
Solubility :	0.183 mg/ml ; 0.00104 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.54

Safety of [ 952479-65-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 952479-65-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 952479-65-1 ]

[ 952479-65-1 ] Synthesis Path-Downstream 1~50

1
[ 755752-82-0 ]
[ 677304-69-7 ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium hydroxide; In methanol; water; at 0 - 20℃; for 18h;	A solution of the indazole (8.30 g, 33.0 mmol) in methanol (100 mL) at 0 C was treated with an 29percent aqueous solution of potassium hydroxide (20 mL). The reaction mixture was allowed to warm to rt and was maintained for 18 h. The pH of the solution was adjusted to 5.5 by the addition of concentrated hydrochloric acid and the volatiles were removed under reduced pressure. The residue was partitioned between brine (100 mL) and ethyl acetate (200 mL) and the aqueous layer was extracted with additional warm ethyl acetate (200 mL). The combined organic extracts were dried over anhydrous sodium sulfate and concentrated. The residue was triturated with ethyl acetate (30 mL) and the solids were isolated by filtration, thus providing 5.86 g (94percent) of the acid
55%		A mixture of 2-amino-3-methylbenzoic acid (15.2 g, 0.10 mol), dimethylformamide (333 mL) and CsCO3 (49 g, 0.15 mol) was stirred at room temperature for about 40 minutes before drop wise addition of iodomethane (14.2 g, 6.2 mL, 0.10 mol) in dimethylformamide ("DMF") (115 mL). The mixture was stirred . at room temperature overnight. The mixture was diluted with water (1 L), and extracted with diethyl ether. The aqueous phase was back extracted with diethyl ether. The combined organic extracts were washed with saturated aqueous NaCI, dried over MgSO4, filtered and concentrated. The resultant material was dried at room temperature/0.5 mmHg to afford methyl 2-amino-3-methylbenzoate (17 g, 100percent).To a solution methyl 2-amino-3-methylbenzoate (16.5 g, 0.10 mol) in CHCI3 (286 mL) was added acetic anhydride (23.5 g, 21.7 mL, 0.23 mol) so as to maintain the internal temperature <40 0C. The mixture was stirred at room temperature for 1 hour before addition of potassium acetate (2.94 g, 30 mmol) and isoamyl nitrite (25.8 g, 30 mL, 0.22 mol). The resultant mixture was heated at reflux overnight. To this was then added methanol (94 mL) and 6 N HCI (94 mL) and the mixture was stirred overnight. The reaction mixture was concentrated to provide an orange solid which was subsequently triturated with ethyl <n="29"/>acetate and the solids were isolated by vacuum filtration. The solids were dried at room temperature/0.5 mmHg to afford methyl 1 H-indazole-7-carboxylate (15.4 g, 88percent). -A solution of methyl 1 H-indazole-7-carboxylate (14.96 g, 84.9 mmol) in methanol (180 ml_) was cooled to 0 0C before addition of 29percent aqueous potassium hydroxide (36 ml_). The ice bath was removed and the reaction mixture was stirred at room temperature overnight. The pH was adjusted to 5.5 using concentrated HCI. The volatiles were removed by vacuum filtration and the resultant material was suspended in water (100 mL) and ethyl acetate (200 mL). The resultant precipitate was isolated by vacuum filtration and rinsed with ethyl acetate. The solids were dried at room temperature/0.5 mmHg to afford the title compound (7.54 g, 55percent).

Reference： [1]Patent: WO2004/29050,2004,A1 .Location in patent: Page 64;65
[2]Patent: WO2008/65508,2008,A1 .Location in patent: Page/Page column 27-28

2
[ 22223-49-0 ]
[ 755752-82-0 ]

Yield	Reaction Conditions	Operation in experiment
68%		To a solution of the ester (17.5 g, 106 mmol) in chloroform (300 mL) was added acetic anhydride (22.6 mL, 239 mmol, 2.3 eq) while maintaining the temperature below 40 C. The reaction mixture was maintained at room temperature for 1 h when potassium acetate (3.00 g, 30.6 mmol, 0.3 eq) and isoamyl nitrite (30.6 mL, 228 mmol, 2.2 eqiv) was added. The reaction mixture was heated at reflux for 24 h and was allowed to cool to room temperature. The reaction mixture was washed with a saturated, aqueous solution of sodium bicarbonate, dried over sodium sulfate, and concentrated. Methanol (100 mL) and 6 N hydrochloric acid (100 mL) were added to the residue and the mixture was maintained for 18 h at rt. The volatiles were removed under reduced pressure and the residue was triturated with ethyl acetate (100 mL). The product was isolated by filteration, washed with ethyl acetate (20 mL), and dried to provide 15.3 g (68%) of methyl 1H-indazole-7-carboxylate hydrochloride. 1H NMR (500 MHz, DMSO-d6) & delta 13.3 (bs, 1H), 8.26 (d, 1H), 8.12 (d, 1H), 8.25 (dd, 1H), 7.27 (t, 1H), 3.97 (s, 3H); MS (APCI) m/z 177 (M+ +1)
47%		A cooled (5 C) solution of sodium nitrite (1.670 g, 24.21 mmol) in water (3.3 mL) was added to a cooled (0 C) solution of methyl 2-amino-3-methylbenzoate (4.00 g, 24.21 mmol) in 50% HBF4 (10 ml). After complete addition the mixture was stirred for 1 hour at room temperature. The resultant precipitate was isolated by filtration and washed with Et2O. The diazonium salt was then added in one portion to a stirred mixture of dried and powdered potassium acetate (4.752 g, 48.42 mmol) and 18-crown-6 (0.32 g, 0.4 mmol) in dry chloroform (40 mL). After 1 hour the precipitate was removed and the filtrate was washed with water (20 mL), dried (MgSO4) and evaporated under reduced pressure. Recrystallization of the residue from heptanes gave the title compound (2.017 g, 47%) as a pale orange powder. mp. 110 - 112 C. 1H NMR (300 MHz, CDCl3) delta 11.54 (s, 1H), 8.14 (d, J = 1.5 Hz, 1H), 8.05 (dd, J = 7.3, 1.0 Hz, 1H), 7.96 (ddd, J = 8.0, 1.5, 1.0 Hz, 1H), 7.21 (dd, J = 8.0, 7.3 Hz, 1H), 4.03 (s, 3H). 13C NMR (75 MHz, CDCl3) delta 166.7, 138.8, 135.0, 129.2, 126.8, 124.5, 120.5, 112.6, 52.5
		To a solution of methyl 2-amino-3-methylbenzoate (13g, 78.7 mmol) in 50OmL of AcOH at 0 0C was slowly added a solution of sodium nitrite (6.5g, 94.2mmol) in 10OmL of water dropwise over 1 hour. The solution was allowed to stir for ON at it afterwhich it was concentrated to one tenth its volume and then neutralized by the slow addition of 5% ammonium hyroxide. The solution was then extracted with EtOAc and the organic phases were then combined, washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The indazole-methyl ester was purified by flash chromotography using 5-25% EtOAc/hexanes to yield 1Og of pure ester. 1H NMR (500 MHz, CDC13): delta 12.5 (bs, IH), 8.2 (s,lH), 8.1 (m, 2H), 7.3 (t, IH), 4.09 (s, 3H). LRMS M+l 177.1.

Reference： [1]Patent: WO2004/29050,2004,A1 .Location in patent: Page 64
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937
[3]Journal of Organic Chemistry,2016,vol. 81,p. 6855 - 6861
[4]Patent: WO2007/121578,2007,A1 .Location in patent: Page/Page column 29
[5]Patent: WO2008/65508,2008,A1

3
[ 37619-23-1 ]
[ 755752-82-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate; isopentyl nitrite; In chloroform;Heating / reflux;	A mixture of 2-amino-3-methylbenzoic acid (15.2 g, 0.10 mol), dimethylformamide (333 mL) and CsCO3 (49 g, 0.15 mol) was stirred at room temperature for about 40 minutes before drop wise addition of iodomethane (14.2 g, 6.2 mL, 0.10 mol) in dimethylformamide ("DMF") (115 mL). The mixture was stirred . at room temperature overnight. The mixture was diluted with water (1 L), and extracted with diethyl ether. The aqueous phase was back extracted with diethyl ether. The combined organic extracts were washed with saturated aqueous NaCI, dried over MgSO4, filtered and concentrated. The resultant material was dried at room temperature/0.5 mmHg to afford methyl 2-amino-3-methylbenzoate (17 g, 100%).To a solution methyl 2-amino-3-methylbenzoate (16.5 g, 0.10 mol) in CHCI3 (286 mL) was added acetic anhydride (23.5 g, 21.7 mL, 0.23 mol) so as to maintain the internal temperature <40 0C. The mixture was stirred at room temperature for 1 hour before addition of potassium acetate (2.94 g, 30 mmol) and isoamyl nitrite (25.8 g, 30 mL, 0.22 mol). The resultant mixture was heated at reflux overnight. To this was then added methanol (94 mL) and 6 N HCI (94 mL) and the mixture was stirred overnight. The reaction mixture was concentrated to provide an orange solid which was subsequently triturated with ethyl <n="29"/>acetate and the solids were isolated by vacuum filtration. The solids were dried at room temperature/0.5 mmHg to afford methyl 1 H-indazole-7-carboxylate (15.4 g, 88%). -A solution of methyl 1 H-indazole-7-carboxylate (14.96 g, 84.9 mmol) in methanol (180 ml_) was cooled to 0 0C before addition of 29% aqueous potassium hydroxide (36 ml_). The ice bath was removed and the reaction mixture was stirred at room temperature overnight. The pH was adjusted to 5.5 using concentrated HCI. The volatiles were removed by vacuum filtration and the resultant material was suspended in water (100 mL) and ethyl acetate (200 mL). The resultant precipitate was isolated by vacuum filtration and rinsed with ethyl acetate. The solids were dried at room temperature/0.5 mmHg to afford the title compound (7.54 g, 55%).

Reference： [1]Patent: WO2008/65508,2008,A1 .Location in patent: Page/Page column 27-28

4
[ 755752-82-0 ]
[ 1476776-55-2 ]
[ 1196713-67-3 ]
[ 1476776-89-2 ]

Reference： [1]Organic Process Research and Development,2014,vol. 18,p. 215 - 227

5
[ 95-53-4 ]
[ 755752-82-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937

6
[ 1132-03-2 ]
[ 755752-82-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937

7
[ 1127-59-9 ]
[ 755752-82-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937

8
[ 4389-45-1 ]
[ 755752-82-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937
[2]Journal of Organic Chemistry,2016,vol. 81,p. 6855 - 6861
[3]Patent: WO2008/65508,2008,A1

9
[ 755752-82-0 ]
N-((1H-indazol-7-yl)methyl)-2-(4-bromo-2,5-dimethoxyphenyl)ethanamine hydrochloride [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937

10
[ 755752-82-0 ]
C₁₈H₁₈BrN₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937

11
[ 755752-82-0 ]
[ 1092961-09-5 ]

Yield	Reaction Conditions	Operation in experiment
73%	With lithium aluminium tetrahydride; In tetrahydrofuran; for 0.5h;	To a solution of <strong>[755752-82-0]methyl 1H-indazole-7-carboxylate</strong> (0.182 g, 1.033 mmol) in dry THF (10 mL) was added a 1.0M solution of LiAlH4 (2.1 mL, 2.10 mmol). The reaction was stirred for 30 minutes and then quenched by successive addition of water (210 muL), 15% NaOH (210 muL) and water (630 muL). The suspension was diluted with THF (10 mL) and there was added MgSO4. The suspension was stirred for 10 minutes and filtered. The filter cake was washed with EtOAc (10 mL) and CHCl3/MeOH (1:1, 10 mL) and the combined filtrates were evaporated under reduced pressure to afford the title compound (0.112 g, 73%) as a white solid. 1H NMR (300 MHz, DMSO-d6) delta 8.05 (s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 6.9 Hz, 1H), 7.06 (dd, J =8.0, 6.9 Hz, 1H), 4.80 (2H, s). 13C NMR (75 MHz, DMSO-d6) delta 133.4, 133.3, 124.8, 122.9, 122.8, 120.1, 118.8, 59.8

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937
[2]Journal of Organic Chemistry,2016,vol. 81,p. 6855 - 6861

12
[ 755752-82-0 ]
1-H-indazole-7-carbaldehyde [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3933 - 3937
[2]Journal of Organic Chemistry,2016,vol. 81,p. 6855 - 6861

13
[ 755752-82-0 ]
3-iodo-1H-indazole-7-carbaldehyde [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 6855 - 6861

14
[ 5471-82-9 ]
[ 755752-82-0 ]

Yield	Reaction Conditions	Operation in experiment
12.6 g	With potassium acetate; acetic acid; isopentyl nitrite; In 1,2-dichloro-ethane; for 24h;Reflux;	Example 9 Compound 16 (20.0g, 0.103mol) in 1,2-dichloroethane was added 100mL, acetic acid 20mL, was added potassium acetate (2.0g, 0.021mol) was dissolved after stirring, isoamyl nitrite (24.1 g of, 0.206 mol), heated to reflux and reacted at this temperature for 24 hours, cooled to room temperature, the reaction was washed with saturated sodium carbonate solution, the solution was evaporated under reduced pressure, 80 mL of ethanol was added to the residual liquid, dropwise under ice after 10mL of concentrated hydrochloric acid was added, and stirred at this temperature for 2 hours, the solid was filtered off to give a pale yellow solid, the resulting solid was added 90 mL of ethyl acetate and saturated sodium carbonate solution was added 100mL, stirred for 1 hour, the organic phase liquid separation, the aqueous phase was washed twice with ethyl acetate (2 * 50mL), the organic phase was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to give a pale yellow solid 12.6g.

Reference： [1]Patent: CN106854176,2017,A .Location in patent: Paragraph 0050; 0051

15
[ 755752-82-0 ]
C₁₆H₂₂ClNO₂ [ No CAS ]
[ 1196713-67-3 ]

Yield	Reaction Conditions	Operation in experiment
	With quinoline; copper(l) iodide; sodium carbonate; In 1-methyl-pyrrolidin-2-one; at 145℃; for 24h;Inert atmosphere;	Example 10 Under nitrogen atmosphere, Compound 17 (5.5g, 0.031mol), compound 12 (10.0g, 0.029mol) in N- methylpyrrolidone was added 70 mL, and added quinoline (400mg, 3.1mmol), sodium carbonate ( 7.7g, 0.073mol), cuprous iodide (450mg, 2.3mmol), was heated to 145 deg.] C for 24 hours, after to room temperature, insoluble matter was filtered off, the filtrate was added 140mL of water, solid precipitated solid was filtered off after drying under reduced pressure (45 ) 8 h to obtain a light yellow solid 9.1g.

Reference： [1]Patent: CN106854176,2017,A .Location in patent: Paragraph 0052-0055

16
[ 755752-82-0 ]
C₁₆H₂₂INO₂ [ No CAS ]
[ 1196713-67-3 ]

Yield	Reaction Conditions	Operation in experiment
	With quinoline; copper(l) iodide; sodium carbonate; In 1-methyl-pyrrolidin-2-one; at 145℃; for 24h;Inert atmosphere;	Example 10 Under nitrogen atmosphere, Compound 17 (5.5g, 0.031mol), compound 12 (10.0g, 0.029mol) in N- methylpyrrolidone was added 70 mL, and added quinoline (400mg, 3.1mmol), sodium carbonate ( 7.7g, 0.073mol), cuprous iodide (450mg, 2.3mmol), was heated to 145 deg.] C for 24 hours, after to room temperature, insoluble matter was filtered off, the filtrate was added 140mL of water, solid precipitated solid was filtered off after drying under reduced pressure (45 ) 8 h to obtain a light yellow solid 9.1g.

Reference： [1]Patent: CN106854176,2017,A .Location in patent: Paragraph 0052-0055

17
[ 755752-82-0 ]
C₁₇H₂₂F₃NO₅S [ No CAS ]
[ 1196713-67-3 ]

Yield	Reaction Conditions	Operation in experiment
	With quinoline; copper(l) iodide; sodium carbonate; In 1-methyl-pyrrolidin-2-one; at 145℃; for 24h;Inert atmosphere;	Example 10 Under nitrogen atmosphere, Compound 17 (5.5g, 0.031mol), compound 12 (10.0g, 0.029mol) in N- methylpyrrolidone was added 70 mL, and added quinoline (400mg, 3.1mmol), sodium carbonate ( 7.7g, 0.073mol), cuprous iodide (450mg, 2.3mmol), was heated to 145 deg.] C for 24 hours, after to room temperature, insoluble matter was filtered off, the filtrate was added 140mL of water, solid precipitated solid was filtered off after drying under reduced pressure (45 ) 8 h to obtain a light yellow solid 9.1g.

Reference： [1]Patent: CN106854176,2017,A .Location in patent: Paragraph 0052-0055

18
[ 755752-82-0 ]
[ 1476776-55-2 ]
[ 1196713-67-3 ]

Yield	Reaction Conditions	Operation in experiment
9.1 g	With quinoline; copper(l) iodide; sodium carbonate; In 1-methyl-pyrrolidin-2-one; at 145℃; for 24h;Inert atmosphere;	Example 10 Under nitrogen atmosphere, Compound 17 (5.5g, 0.031mol), compound 12 (10.0g, 0.029mol) in N- methylpyrrolidone was added 70 mL, and added quinoline (400mg, 3.1mmol), sodium carbonate ( 7.7g, 0.073mol), cuprous iodide (450mg, 2.3mmol), was heated to 145 deg.] C for 24 hours, after to room temperature, insoluble matter was filtered off, the filtrate was added 140mL of water, solid precipitated solid was filtered off after drying under reduced pressure (45 ) 8 h to obtain a light yellow solid 9.1g.

Reference： [1]Patent: CN106854176,2017,A .Location in patent: Paragraph 0052; 0053

19
[ 755752-82-0 ]
2-[4-((3S)-3-piperidinyl)phenyl]-2H-indazole-7-carboxamide p-toluenesulfonate [ No CAS ]

Reference： [1]Patent: CN106854176,2017,A
[2]Patent: CN106854176,2017,A
[3]Patent: CN106854176,2017,A

20
[ 755752-82-0 ]
[ 1031413-43-0 ]

Reference： [1]Patent: WO2008/65508,2008,A1

21
[ 755752-82-0 ]
[ 1031413-69-0 ]

Reference： [1]Patent: WO2008/65508,2008,A1

22
[ 755752-82-0 ]
(racemic)-6-(1-(4-(trifluoromethoxy)benzyl)-1H-indazole-7-carboxamido)spiro[3.3]heptane-2-carboxylic acid [ No CAS ]

Reference： [1]Patent: US2019/315712,2019,A1

23
[ 755752-82-0 ]
1-(4-(trifluoromethoxy)benzyl)-1H-indazole-7-carboxylic acid [ No CAS ]

Reference： [1]Patent: US2019/315712,2019,A1

24
[ 755752-82-0 ]
(racemic)-methyl 6-(1-(4-(trifluoromethoxy)benzyl)-1H-indazole-7-carboxamido)spiro[3.3]heptane-2-carboxylate [ No CAS ]

Reference： [1]Patent: US2019/315712,2019,A1

25
[ 755752-82-0 ]
[ 50824-05-0 ]
methyl 1-(4-(trifluoromethoxy)benzyl)-1H-indazole-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 0 - 22℃; for 16h;	In a round-bottom flask equipped with a magnetic stir bar was suspended <strong>[755752-82-0]methyl 1H-indazole-7-carboxylate</strong> (1.0 equiv, Combi-Blocks, CAS 755752-82-0) and cesium carbonate (3 equiv) in DMF (0.71 M). This suspension was cooled to 0 C. and treated with neat 4-(trifluoromethoxy)benzyl bromide (1.2 equiv, Aldrich, CAS 50824-05-0) drop-wise over a period of 5 minutes. The resulting reaction mixture was allowed to 22 C. over 16 hours. The reaction was then carefully quenched with the addition of ice-water and extracted with tert-butyl methyl ether. The combined organic extracts were washed further with water and brine, dried over MgSO4, and filtered. Concentration of the filtrate thus obtained under vacuum furnished the crude reaction product as a golden yellow oil. Purification by column chromatography through silica gel on the Teledyne ISCO Rf eluting with 10% to 100% EtOAc in hexanes as a gradient afforded the title compound.

Reference： [1]Patent: US2019/315712,2019,A1 .Location in patent: Paragraph 1210; 1211

26
[ 755752-82-0 ]
1-([1,1'-biphenyl]-4-yl)ethan-1,2,2,2-d₄-1-ol [ No CAS ]
methyl 1-(1-([1,1'-biphenyl]-4-yl)ethyl-1,2,2,2-d₄)-1H-indazole-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 70℃; for 18h;Cooling with ice;	Into a reaction vail equipped with a magnetic stir bar was added 1-([1,1?-biphenyl]-4-yl)ethan-1,2,2,2-d4-1-ol (1.5 equiv), <strong>[755752-82-0]methyl 1H-indazole-7-carboxylate</strong> (1.0 equiv), triphenylphosphine (1.3 equiv) and THF (0.3 M). The mixture was cooled over an ice bath, added diisopropyl azodicarboxylate (1.2 equiv) dropwise and stirred for 10 minutes as the reactants dissolved. After this time, the cooling bath was removed and the mixture was heated at 70 C. for 18 hours. LC-MS indicated completion of reaction. The reaction mixture was loaded onto a silica gel pre-cartridge and dried. Purification by column chromatography through silica gel on the Teledyne ISCO Rf (gradient elution with 0% to 60% EtOAc in hexanes) afforded the desired product (28% yield).

Reference： [1]Patent: US2019/315712,2019,A1 .Location in patent: Paragraph 1146; 1147

27
[ 952479-65-1 ]
1-benzyl-1H-indazole-7-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 80 °C / Inert atmosphere 2: water; lithium hydroxide / methanol / 20 °C